The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass.

BACKGROUND: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. OBJECTIVES: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. SETTING: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. METHODS: Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www. CLINICALTRIALS: gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. RESULTS: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. CONCLUSION: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.

Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis.

BACKGROUND: There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy. METHODS: This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score-matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections. RESULTS: This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups. CONCLUSIONS: Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.

Design and Implementation of an Analgesia, Sedation, and Paralysis Order Set to Enhance Compliance of pro re nata Medication Orders with Joint Commission Medication Management Standards in a Pediatric ICU.

BACKGROUND: The use of pro re nata (PRN) medication orders increases nursing flexibility and efficiency of bedside patient care. However, misuse and/or ambiguity of PRN medication orders may increase the propensity for medication errors. The Joint Commission has Medication Management (MM) standards to mitigate such risks. This quality improvement study with a pre-post design aimed to increase compliance of PRN sedative and analgesic orders with use of failure mode and effects analysis (FMEA) and human factors risk assessment methodologies in a pediatric ICU (PICU). METHODS: Staff education and a PICU analgesia, sedation, and paralysis order set, with predefined PRN orders, were implemented to enhance PRN medication compliance with Joint Commission MM standards. The primary goal was to achieve and maintain a weekly average compliance of ≥ 90%. Proportions of compliant PRN analgesic and sedative orders before and after interventions were compared. RESULTS: Weekly average PRN orders compliance increased from 62.0% ± 9.2% to 77.7% ± 10.1% after staff education was implemented (p = 0.013). After order set implementation, weekly average compliance further increased to 93.2% ± 3.6% (p < 0.0001) and remained > 90% until the end of the study period. CONCLUSION: Interdisciplinary synthesis using FMEA and human factors risk assessment is effective for identifying system failure modes associated with Joint Commission MM standard noncompliance. Implementation of an order set with forced functionality to include order information compliant with Joint Commission MM standards can enhance and maintain Joint Commission-compliant PRN medication orders.

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report.

The novel coronavirus disease 2019 (COVID-19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID-19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID-19 pneumonia, and despite completing a 5-day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off-label, single-dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID-19. Future investigation of the effects of immunomodulators among transplant recipients with COVID-19 infection will be important.

A Department of Medicine Infrastructure for Patient Safety and Clinical Quality Improvement.

Payers, providers, and patients increasingly recognize the importance of quality and safety in health care. Academic Departments of Medicine can advance quality and safety given the large populations they serve and the broad spectrum of diseases they treat. However, there are only few detailed examples of how quality and safety can be organized. This article describes a practical model at The Johns Hopkins Hospital Department of Medicine and details its structure and operation within a large academic health system. It is based on a fractal model that integrates multiple smaller units similar in structure (composition of faculty/staff), process (use of similar tools), and approach (using a common framework to address issues). This organization stresses local, multidisciplinary leadership, facilitates horizontal connections for peer learning, and maintains vertical connections for broader accountability.

Increasing Advance Care Planning Completion at an Academic Internal Medicine Outpatient Clinic.

BACKGROUND: We sought to increase advance care planning (ACP) completion at an academic internal medicine clinic through an electronic health record. MEASURES: Number of eligible patients who completed a form of ACP. INTERVENTION: Multidisciplinary team approach with engagement from providers and clinic staff; implemented informational letter and appropriate forms to eligible patients before appointment; informational video and provider reminders at time of appointment. OUTCOMES: Of 480 eligible patients, 327 (68%) completed one or more forms of ACP or had a discussion with their provider. Discussed but not completed was highest (53%). The three types of ACP completed were 1) a state-formatted advance directive form (47%), 2) Medical Orders for Life-Sustaining Treatment (45%), and 3) power of attorney designation (8%). CONCLUSIONS: Implementation of a multi-disciplinary approach can facilitate ACP. However, challenges still arise because in more than half of the cases, advance care efforts led only to a discussion.

A Model for the Departmental Quality Management Infrastructure Within an Academic Health System.

As quality improvement and patient safety come to play a larger role in health care, academic medical centers and health systems are poised to take a leadership role in addressing these issues. Academic medical centers can leverage their large integrated footprint and have the ability to innovate in this field. However, a robust quality management infrastructure is needed to support these efforts. In this context, quality and safety are often described at the executive level and at the unit level. Yet, the role of individual departments, which are often the dominant functional unit within a hospital, in realizing health system quality and safety goals has not been addressed. Developing a departmental quality management infrastructure is challenging because departments are diverse in composition, size, resources, and needs.In this article, the authors describe the model of departmental quality management infrastructure that has been implemented at the Johns Hopkins Hospital. This model leverages the fractal approach, linking departments horizontally to support peer and organizational learning and connecting departments vertically to support accountability to the hospital, health system, and board of trustees. This model also provides both structure and flexibility to meet individual departmental needs, recognizing that independence and interdependence are needed for large academic medical centers. The authors describe the structure, function, and support system for this model as well as the practical and essential steps for its implementation. They also provide examples of its early success.

Provider-to-Provider Communication during Transitions of Care from Outpatient to Acute Care: A Systematic Review.

BACKGROUND: Most research on transitions of care has focused on the transition from acute to outpatient care. Little is known about the transition from outpatient to acute care. We conducted a systematic review of the literature on the transition from outpatient to acute care, focusing on provider-to-provider communication and its impact on quality of care. METHODS: We searched the MEDLINE, CINAHL, Scopus, EMBASE, and Cochrane databases for English-language articles describing direct communication between outpatient providers and acute care providers around patients presenting to the emergency department or admitted to the hospital. We conducted double, independent review of titles, abstracts, and full text articles. Conflicts were resolved by consensus. Included articles were abstracted using standardized forms. We maintained search results via Refworks (ProQuest, Bethesda, MD). Risk of bias was assessed using a modified version of the Downs' and Black's tool. RESULTS: Of 4009 citations, twenty articles evaluated direct provider-to-provider communication around the outpatient to acute care transition. Most studies were cross-sectional (65%), conducted in the US (55%), and studied communication between primary care and inpatient providers (62%). Of three studies reporting on the association between communication and 30-day readmissions, none found a significant association; of these studies, only one reported a measure of association (adjusted OR for communication vs. no communication, 1.08; 95% CI 0.92-1.26). DISCUSSION: The literature on provider-to-provider communication at the transition from outpatient to acute care is sparse and heterogeneous. Given the known importance of communication for other transitions of care, future studies are needed on provider-to-provider communication during this transition. Studies evaluating ideal methods for communication to reduce medical errors, utilization, and optimize patient satisfaction at this transition are especially needed.

Changes to inpatient versus outpatient hospitalization: Medicare's 2-midnight rule.

Outpatient versus inpatient status determinations for hospitalized patients impact how hospitals bill Medicare for hospital services. Medicare policies related to status determinations and the Recovery Audit Contractor (RAC) program charged with postpayment review of such determinations are of increasing concern to hospitals and physicians. We present an overview and discussion of these policies, including the recent 2-midnight rule, the effect on status determinations by the RAC program, and other recent and pertinent legislative and regulatory activity. Finally, we discuss the future direction of Medicare status determination policies and the RAC program, so that physicians and other healthcare providers caring for hospitalized Medicare beneficiaries may better understand these important and dynamic topics.

The power of involving house staff in quality improvement: an interdisciplinary house staff-driven vaccination initiative.

Immunization for influenza and pneumococcal pneumonia were incorporated into The Joint Commission "global immunization" core measure January 1, 2012. The authors' hospital chose to adhere strictly to guidelines to avoid overvaccination. An immunization order set was created to aid appropriate ordering practices. In spite of this effort, compliance rates remained below the goal. The objective was to improve compliance with inpatient vaccination core measures to >96%. An educational slide set was created and distributed by the Housestaff Patient Safety and Quality Council (HPSQC). A competition was established among departments. Finally, the HPSQC partnered with quality improvement staff to improve communication and optimize concurrent review processes. The average compliance prior to the HPSQC vaccination initiative was 78% for pneumococcal pneumonia and 84% for influenza; average compliance in the months following the intervention was 96% and 97.5%, respectively. This project yielded significant improvement in compliance with vaccination core measures.

Making general internal medicine research relevant to the older patient with multiple chronic comorbidities.

General Internal Medicine research evolves in response to the needs of the patients to whom we provide care. Currently, many studies exclude older adults who deeply affect the clinical care of this population. With the number of older adults increasing, creating research protocols that include older adults with multiple chronic comorbidities is imperative. Through funding from the Association of Specialty Physicians, a working group of aging-responsive researchers from the Society of General Internal Medicine was convened to tackle this issue. The goal of this article is threefold: 1) to shed light on the current exclusion of older adults in research; 2) to identify and propose research protocol solutions for overcoming barriers to including older adults in research; and 3) to provide suggestions for research funding. The extent to which these recommendations can create change depends greatly on our researcher colleagues. By embracing these challenges, we hope that the care provided to older adults with multiple chronic conditions will no longer be extrapolated, but become evidence-based.

Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery.

OBJECTIVE: To estimate the risks and benefits associated with continuation of anticoagulants or antiplatelet medication use before cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Patients 50 and older scheduled for 19,283 cataract surgeries at nine centers in the United States and Canada between June 1995 and June 1997. INTERVENTION: None. MAIN OUTCOME MEASURES: Intraoperative and postoperative (within 7 days) retrobulbar hemorrhage, vitreous or choroidal hemorrhage, hyphema, transient ischemic attack (TIA), stroke, deep vein thrombosis, myocardial ischemia, and myocardial infarction. RESULTS: Before cataract surgery 24.2% and 4.0% of patients routinely used aspirin and warfarin, respectively. Among routine users, 22.5% of aspirin users and 28.3% of warfarin users discontinued these medications before surgery. The rates of stroke, TIA, or deep vein thrombosis were 1.5/1000 among those who did not use aspirin or warfarin and 3.8/1000 surgeries among routine users of aspirin and warfarin who continued their medication before surgery. The rate was 1 event per 1000 surgeries among those who discontinued aspirin use (relative risk = 0.7, 95% confidence interval = 0.1-5.9). There were no events among warfarin users who discontinued use. The rates of myocardial infarction or ischemia were 5.1/1000 surgeries (aspirin) and 7.6/1000 surgeries (warfarin) among routine continuous users and no different from those of routine users who discontinued use. CONCLUSIONS: The risks of medical and ophthalmic events surrounding cataract surgery were so low that absolute differences in risk associated with changes in routine anticoagulant or antiplatelet use were minimal.

Limitations of D-dimer testing in unselected inpatients with suspected venous thromboembolism.

PURPOSE: To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients. METHODS: We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic evaluation for possible venous thromboembolism. We included patients with a history of malignancy, recent surgery, thrombosis, and anticoagulation treatment. C-reactive protein levels were assayed as a measure of inflammation. RESULTS: Of 45 patients with radiographically proven proximal deep venous thrombosis or pulmonary embolism, 43 had elevated D-dimer levels by enzyme-linked immunosorbent assay (ELISA) (sensitivity, 96%); the specificity of the test was 23% (36/157). The qualitative non-ELISA tests had higher specificities, but their sensitivities were <70%. Nineteen patients (42%) with thrombosis had false-negative D-dimer tests by at least one assay. The specificity of the tests decreased with increasing duration of hospitalization, increasing age, and increasing C-reactive protein levels. D-dimer testing had little or no utility in distinguishing patients with thrombosis from those without in patients who had been hospitalized for more than 3 days, were older than 60 years, or had C-reactive protein levels in the highest quartile. CONCLUSION: In unselected inpatients, D-dimer testing has limited clinical utility because of its poor specificity. This is particularly true for older patients, those who have undergone prolonged hospitalization, and those with markedly elevated C-reactive protein levels. In some patient subsets, a negative non-ELISA D-dimer test cannot discriminate between inpatients with and without thrombosis.

Perioperative medication management.

One of the consultant's roles is to make recommendations regarding the use of medications in the perioperative period. Unfortunately, the data in this area are often insufficient to provide evidence-based recommendations. In this article, we have provided advice considering the pharmacokinetics of the drug, the effect on the primary disease of stopping medications, and the effect of the medication on perioperative risk, including potential drug interactions with anesthetic agents.

A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers.

BACKGROUND: With the expiration of the patent on albuterol metered-dose inhalers (MDIs) in 1989, methods to assess in vivo bioequivalence of generic formulations required investigation. OBJECTIVE: In an effort to develop a sensitive method to document bioequivalence, bronchoprovocation with methacholine chloride was used to assess the dose-response relationship of albuterol as delivered by MDI. Sensitivity was assessed in terms of magnitudes of ED(50), the estimated albuterol dose required to achieve 50 % of the fitted maximal value of the pharmacodynamic effect above baseline, and change in response as a function of dose, with emphasis on 1 and 2 actuations. METHODS: On separate study days, 15 nonsmokers with mild asthma received randomized nominal albuterol doses of 0 to 576 microg by using specially manufactured MDI canisters. FEV(1) was measured 15 minutes after MDI dosing. Serially increasing doses of methacholine were administered, and FEV(1) was measured after each methacholine dose until a 20 % decrease in FEV(1) (PD(20)) was achieved. RESULTS: Mean PD(20) values after use of each of the albuterol-containing MDIs were significantly greater than either mean screening or mean placebo PD(20) values (P <.05). Mean responses and most individual subject responses to 1 and 2 actuations (90 and 180 microg) of albuterol MDI were within the sensitive region of the dose- response curve. The mean estimated ED(50) value on the basis of nonlinear mixed effect modeling was 119.2 microg (range, 33.3-337.1 microg), with an intersubject percentage coefficient of variation of 69.0 %. CONCLUSIONS: The methacholine bronchoprovocation model is safe and useful in the study of albuterol MDI dose-response in asthmatic subjects. Bronchoprovocation studies may be used for determination of bioequivalence of multisource albuterol MDI products.